Sosei highlights data from QVA149 clinical trials on COPD

Sosei Group Corporation ("Sosei"; TSE Mothers Index: 4565) highlights that further data from the once-daily chronic obstructive pulmonary disease (COPD) clinical trial programs were presented today by Novartis at the European Respiratory Society (ERS) Congress. Overall, Novartis presented 14 abstracts, including data from the investigational QVA149 (fixed-dose combination of indacaterol maleate / glycopyrronium bromide) IGNITE Phase III clinical trial program, and the glycopyrronium bromide (Seebri^® Breezhaler^®) GLOW Phase III clinical trial program.

Among the data presented, three new studies from the investigational QVA149 IGNITE Phase III clinical trial program (SHINE, ILLUMINATE and ENLIGHTEN) demonstrated that QVA149 significantly improved lung function compared to other COPD therapies. Data from the GLOW program showed that glycopyrronium 50 mcg once daily provided rapid and sustained bronchodilation, and reduced exacerbations and symptoms when compared to placebo, similar to the levels observed with open-label (OL) tiotropium 18 mcg.

IGNITE data demonstrated the efficacy of the dual-bronchodilator QVA149 (indacaterol maleate / glycopyrronium bromide) and showed a superior effect on lung function and patient-reported outcomes versus comparators

SHINE met its primary endpoint by demonstrating that once-daily QVA149 110/50 mcg improved lung function as measured by trough FEV₁ compared to once-daily indacaterol maleate 150 mcg (+70mL above indacaterol alone; p<0.001) and once-daily glycopyrronium 50 mcg (+90mL above glycopyrronium alone; p<0.001). QVA149 110/50 mcg is an investigational inhaled dry-powder fixed-dose combination medication that provides the equivalent amount of indacaterol as Onbrez (indacaterol maleate) 150 mcg along with glycopyrronium 50 mcg.  QVA149 was also more effective at improving lung function compared to OL tiotropium 18 mcg (+80mL above tiotropium; p<0.001) and placebo (+200mL; p<0.001). Mean peak FEV₁ at Week 26 was also significantly higher with QVA149 compared to placebo (+330mL, p<0.001), indacaterol 150 mcg (+120mL; p<0.001), glycopyrronium 50 mcg (+130mL; p<0.001) and OL tiotropium 18 mcg (+130mL; p<0.001). Mean FEV₁ area under the curve (AUC) for 0-24hr at Week 26 was significantly higher with QVA149 compared to placebo (+320mL, p<0.001), indacaterol 150 mcg (+110mL; p<0.001), glycopyrronium 50 mcg (+110mL; p<0.001) and OL tiotropium 18 mcg (+110mL; p<0.001).

The results also showed that QVA149 improved breathlessness measured by the transition dyspnea index or TDI (p<0.001 versus placebo; p<0.05 versus OL tiotropium 18 mcg), increased health-related quality of life (HRQoL) measured by the St George's Respiratory Questionnaire or SGRQ (p<0.01 versus placebo; p<0.05 versus OL tiotropium 18 mcg) and reduced rescue medication use (p<0.001 versus both placebo and OL tiotropium 18 mcg). QVA149 was superior to indacaterol 150 mcg and glycopyrronium 50 mcg at reducing use of rescue medication (p<0.05 and p<0.001 respectively) and also provided numerically higher improvements in breathlessness and HRQoL compared to indacaterol 150 mcg and glycopyrronium 50 mcg.

ILLUMINATE compared QVA149 110/50 mcg to the twice-daily LABA/ICS salmeterol/fluticasone 50/500 mcg head-to-head over 26 weeks in patients with COPD. The study met its primary endpoint by demonstrating that the mean FEV₁ area under the curve (AUC) for 0-12hr at Week 26 was significantly higher with QVA149 compared to salmeterol/fluticasone 50/500 mcg (+140mL; p<0.001). Mean FEV₁ AUC_0-12h was also significantly higher with QVA149 versus salmeterol/fluticasone 50/500 mcg at Day 1 (+70mL; p<0.001) and Week 12 (+120mL; p<0.001). The ILLUMINATE trial also demonstrated that QVA149, in comparison to salmeterol/fluticasone 50/500 mcg, significantly improved breathlessness measured by TDI (p=0.003) and reduced rescue medication use (p=0.019) over 26 weeks.

ENLIGHTEN demonstrated the efficacy of QVA149 at improving lung function over a 52-week period by showing that QVA149 increased FEV₁ and forced vital capacity (FVC) versus placebo at Day 1 and Weeks 3, 6, 12, 26, 39 and 52 (p<0.001). At Week 52, the mean difference in FEV₁ compared to placebo at 60 minutes post-dose was +257mL (p<0.001).

QVA149 was generally well tolerated in the SHINE, ILLUMINATE and ENLIGHTEN trials with an incidence of adverse events that was similar between respective groups.

GLOW pooled analyses demonstrated that investigational glycopyrronium increased lung function, improved patient outcomes compared to placebo

Results of the first pooled analysis of GLOW1 and GLOW2 data demonstrated that patients on glycopyrronium 50 mcg experienced rapid, sustained and clinically meaningful bronchodilation over 52 weeks. The improvement in FEV₁ was seen within five minutes after the first dose on Day 1 (+90mL at 5 minutes and +144mL at 15 minutes versus placebo; p<0.001) and was sustained throughout the 52-week period (p<0.001 vs. placebo). FEV₁ AUC for 0-4h, 0-12h, 0-24h and 12-24h for glycopyrronium 50 mcg was statistically significantly greater than placebo (p<0.05) and numerically greater than OL tiotropium 18 mcg (an exploratory arm in GLOW2) when compared to placebo on Day 1 and Weeks 12, 26 and 52.  When compared to placebo, glycopyrronium 50 mcg was also numerically higher than OL tiotropium 18 mcg versus placebo at all-time points for trough FEV₁ (Day 1 and Weeks 12, 26 and 52).

The second pooled analysis of GLOW1 and GLOW2 data found that for patients taking glycopyrronium 50 mcg, the time to first moderate/severe exacerbation was significantly prolonged compared to placebo at both Week 26 (hazard ratio [HR] 0.64; p<0.001) and Week 52 (HR 0.67; p<0.001). The results were comparable in patients treated with OL tiotropium 18 mcg. Glycopyrronium 50 mcg also significantly lowered the rate of moderate/severe exacerbations versus placebo at Weeks 26 and 52 (both rate ratio [RR] 0.66; p<0.005).

Glycopyrronium 50 mcg improved breathlessness measured by TDI (p<0.05) and health-related quality of life measured by SGRQ (p<0.001) at Weeks 26 and 52. The results were similar to OL tiotropium 18 mcg compared to placebo.